Human P2Y₁₁ Expression Level Affects Human P2X7 Receptor-Mediated Cell Death.

ABSTRACT: Adenosine triphosphate (ATP) is known to induce cell death in T lymphocytes at high extracellular concentrations. CD4⁺ and CD8⁺ T lymphocytes have a differential response to ATP, which in mice is due to differences in the P2X7 receptor expression levels. By contrast, we observed that the difference in human CD4⁺ and CD8⁺ T lymphocyte response toward the synthetic ATP-analog BzATP is not explained by a difference in human P2X7 receptor expression. Rather, the BzATP-induced human P2X7 receptor response in naïve and immune-activated lymphocyte subtypes correlated with the expression of another ATP-binding receptor: the human P2Y₁₁ receptor. In a recombinant expression system, the coexpression of the human P2Y₁₁ receptor counteracted BzATP-induced human P2X7 receptor-driven lactate dehydrogenase release (a marker of cell death) and pore formation independent of calcium signaling. A mutated non-signaling human P2Y₁₁ receptor had a similar human P2X7 receptor-inhibitory effect on pore formation, thus demonstrating that the human P2X7 receptor interference was not caused by human P2Y₁₁ receptor signaling. In conclusion, we demonstrate an important species difference in the ATP-mediated cell death between mice and human cells and show that in human T lymphocytes, the expression of the human P2Y₁₁ receptor correlates with human P2X7 receptor-driven cell death following BzATP stimulation.

SUBMITTER: Dreisig K 

PROVIDER: S-EPMC6002484 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature